Genetic differences have been proposed to play a strong role in risk of death from infectious diseases. The study base of 44,005 included all same-sex twin pairs born in 1870-2001, with both twins alive on January 1, 1943, or those born thereafter. Cause of death was obtained from the Danish Cause of Death Register and was available for 18,359 deaths. The authors classified death due to infections by 3 definitions (narrow, broader, and broadest) and calculated concordance rates for same-sex monozygotic and dizygotic twin pairs. Heritability was estimated by using structural equation models. When the 3 definitions were applied, 211 (1.1%), 1,089 (5.9%), and 2,907 (15.8%) deaths, respectively, were due to infections. The probandwise concordance rates for monozygotic twin pairs were consistently higher than for dizygotic twin pairs regardless of the definition (9% vs. 0% (P = 0.04), 10% vs. 3% (P <0.01), and 19% vs. 15% (P = 0.07), respectively). For the broader and broadest definitions, heritability was 40% (95% confidence interval: 12, 50) and 19% (95% confidence interval: 3, 35), respectively. The concordance rates were generally low, and, although a genetic influence on the risk of death from infectious diseases could be demonstrated, the absolute effect of the genetic component on mortality was small.